Changes in skeletal muscle protein quantity and quality in heart failure contribute to decreased muscle strength and endurance and increased morbidity and mortality. Our overall hypothesis is that alterations in skeletal muscle protein metabolism promote changes in the quantity and quality of skeletal muscle protein. Skeletal muscle protein metabolism measurements will be made on cachectic and non-cachectic heart failure patients and healthy controls. In this experimental design, alterations in skeletal muscle protein metabolism specific to cachectic patients represent possible mechanisms contributing to changes in skeletal muscle protein quantity and quality. Non-cachectic heart failure patients will serve as a diseased control group and healthy controls as a non-diseased control group. Our primary goal is to determine the pathophysiological mechanisms underlying the loss of skeletal muscle mass (i.e., quantity) in patients with chronic heart failure. Our hypothesis is that increased skeletal muscle protein catabolism in the postabsorptive state and reduced skeletal muscle protein anabolism in the postprandial state promote skeletal muscle atrophy in heart failure patients. We will measure skeletal muscle protein balance (i.e., synthesis and breakdown) using a combination of the forearm balance model and stable isotope tracer techniques under postabsorptive (24 hour fast) and simulated-postprandial conditions (euglycemic hyperinsulinemia with concomitant hyperaminoacidemia). Our secondary goal is to measure and compare the synthesis rate of skeletal muscle myosin heavy chain between heart failure patients and healthy controls (i.e., muscle quality). Our hypothesis is that myosin heavy chain synthesis will be reduced in cachectic and non-cachectic heart failure patients compared to healthy controls. The fractional synthetic rate of myosin heavy chain will be assessed by measuring the incorporation of [1,2-13C2]leucine into skeletal muscle protein. These experiments will provide new information regarding the pathophysiological mechanisms responsible for the loss of skeletal muscle protein quality and quantity in heart failure patients.